PCAF-Mediated Histone Acetylation Promotes Replication Fork Degradation by MRE11 and EXO1 in BRCA-Deficient Cells.

Stabilization of stalled replication forks is a prominent mechanism of PARP (Poly(ADP-ribose) Polymerase) inhibitor (PARPi) resistance in BRCA-deficient tumors. Epigenetic mechanisms of replication fork stability are emerging but remain poorly understood. Here, we report the histone acetyltransferase PCAF (p300/CBP-associated) as a fork-associated protein that promotes fork degradation in BRCA-deficient cells by acetylating H4K8 at stalled replication forks, which recruits MRE11 and EXO1. A H4K8ac binding domain within MRE11/EXO1 is required for their recruitment to stalled forks. Low PCAF levels, which we identify in a subset of BRCA2-deficient tumors, stabilize stalled forks, resulting in PARPi resistance in BRCA-deficient cells. Furthermore, PCAF activity is tightly regulated by ATR (ataxia telangiectasia and Rad3-related), which phosphorylates PCAF on serine 264 (S264) to limit its association and activity at stalled forks. Our results reveal PCAF and histone acetylation as critical regulators of fork stability and PARPi responses in BRCA-deficient cells, which provides key insights into targeting BRCA-deficient tumors and identifying epigenetic modulators of chemotherapeutic responses.

Natural course of talar avascular necrosis during short-term follow-up and factors associated with Disease progression.

BACKGROUND: This retrospective cohort study aimed to investigate the natural history of talar avascular necrosis (AVN) during short-term outpatient follow-up and to identify the risk factors for progression to collapse and arthritic changes. METHODS: Thirty-four cases of talar AVN from 34 patients (15 males, 19 females) were included. The mean age of the patients was 48.9 years (SD 16.0 years) and the mean follow-up period was 39.5 months (SD 42.0 months). The patients were divided into two groups i.e., progression and non-progression groups. The progression group consisted of those who showed aggravation of the Ficat stage during the follow-up period or advanced arthritis of the ankle joint (Ficat stage 4) at presentation. Demographic data and information regarding BMI, medical comorbidities, trauma history, bilaterality, and location of the lesion (shoulder vs. non-shoulder lesions) were collected. Following the univariate analysis, a binary logistic regression analysis was performed. RESULTS: The location of the talar AVN was the only significant factor (p = 0.047) associated with disease progression. A total of 14.3% (2 of 14) of the central (non-shoulder) talar AVN lesions showed progression, while 50% (10 of 20) of shoulder lesions aggravated during follow-up. Age, sex, bilaterality, medical comorbidities, and trauma history were not associated with progressive talar collapse or subsequent arthritic changes in talar AVN. CONCLUSIONS: Conservative treatment should be considered for a central lesion of the talar AVN because it tends to remain stable without progression. A more comprehensive study with a larger study population is required to establish the surgical indications for talar AVN. LEVEL OF EVIDENCE: Prognostic level III.

Postoperative Stability in Displaced Ankle Fractures With Concomitant Ligamentous Injuries.

Ankle instability, which can be attributed to either the deltoid or lateral ligamentous complex, may be both a cause and a consequence of ankle fractures. This study aimed to assess postoperative ankle instability in patients with displaced ankle fractures. A total of 54 patients with displaced ankle fractures were included. Malleolar fractures were surgically reduced and fixated, and if necessary, the syndesmosis was stabilized. Concomitant deltoid injuries were left unrepaired. Ankle stress radiographs were taken approximately 25.4 months after surgery, with a standard deviation of 20.5 months. Radiographic measurements included the tibiotalar tilt angle (TT) on varus stress view, anterior translation of the talus (AT) on the anterior drawer view, and the medial clear space (MC) and tibiotalar tilt angle on the valgus stress view. These measurements were compared between the injured and the noninjured contralateral ankle for all patients as well as in a subgroup of 19 patients with concomitant deltoid and syndesmosis injuries. There were no significant differences in Varus TT (p = .675, p = .394), AT (p = .516, p = .967), Valgus MC (p = .190, p = 0.498), and Valgus TT (p = .173, p = .442) between the injured and noninjured ankles in the whole group of patients as well as in the subgroup of patients with concomitant deltoid and syndesmosis injuries. Patients with displaced ankle fractures exhibited radiographically stable ankles postoperatively. Syndesmosis fixation without deltoid ligament repair is a viable treatment option for achieving ankle stability postoperatively in fractures with both ligament injuries.

Explainable Model Using Shapley Additive Explanations Approach on Wound Infection after Wide Soft Tissue Sarcoma Resection: "Big Data" Analysis Based on Health Insurance Review and Assessment Service Hub.

Background and Objectives: Soft tissue sarcomas represent a heterogeneous group of malignant mesenchymal tissues. Despite their low prevalence, soft tissue sarcomas present clinical challenges for orthopedic surgeons owing to their aggressive nature, and perioperative wound infections. However, the low prevalence of soft tissue sarcomas has hindered the availability of large-scale studies. This study aimed to analyze wound infections after wide resection in patients with soft tissue sarcomas by employing big data analytics from the Hub of the Health Insurance Review and Assessment Service (HIRA). Materials and Methods: Patients who underwent wide excision of soft tissue sarcomas between 2010 and 2021 were included. Data were collected from the HIRA database of approximately 50 million individuals' information in the Republic of Korea. The data collected included demographic information, diagnoses, prescribed medications, and surgical procedures. Random forest has been used to analyze the major associated determinants. A total of 10,906 observations with complete data were divided into training and validation sets in an 80:20 ratio (8773 vs. 2193 cases). Random forest permutation importance was employed to identify the major predictors of infection and Shapley Additive Explanations (SHAP) values were derived to analyze the directions of associations with predictors. Results: A total of 10,969 patients who underwent wide excision of soft tissue sarcomas were included. Among the study population, 886 (8.08%) patients had post-operative infections requiring surgery. The overall transfusion rate for wide excision was 20.67% (2267 patients). Risk factors among the comorbidities of each patient with wound infection were analyzed and dependence plots of individual features were visualized. The transfusion dependence plot reveals a distinctive pattern, with SHAP values displaying a negative trend for individuals without blood transfusions and a positive trend for those who received blood transfusions, emphasizing the substantial impact of blood transfusions on the likelihood of wound infection. Conclusions: Using the machine learning random forest model and the SHAP values, the perioperative transfusion, male sex, old age, and low SES were important features of wound infection in soft-tissue sarcoma patients.

CGV: Cancer Genome Viewer, a web service for integrative cancer genome and pharmacogenomic data analysis.

MOTIVATION: Multi-omic profiling data, such as The Cancer Genome Atlas and pharmacogenomic data, facilitate research into cancer mechanisms and drug development. However, it is not easy for researchers to connect, integrate and analyze huge and heterogeneous data, which is a major obstacle to the utilization of cancer genomic data. RESULTS: We developed Cancer Genome Viewer (CGV), a user-friendly web service that provides functions to integrate and visualize cancer genome data and pharmacogenomic data. Users can easily select and customize the samples to be analyzed with the pre-defined selection options for patients' clinic-pathological features from multiple datasets. Using the customized dataset, users can perform subsequent data analyses comprehensively, including gene set analysis, clustering or survival analysis. CGV also provides pre-calculated drug response scores from pharmacogenomic data, which may facilitate the discovery of new cancer targets and therapeutics. AVAILABILITY AND IMPLEMENTATION: CGV web service is implemented with the R Shiny application at http://cgv.sysmed.kr and the source code is freely available at https://git.sysmed.kr/sysmed_public/cgv. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Radiographic Measurements Associated With Ankle Power Generation During Gait in Patients With Cerebral Palsy.

BACKGROUND: Pes planovalgus (PV) deformity accounts for lever arm dysfunction and compromises gait in patients with cerebral palsy (CP). However, the association between ankle power generation and radiographic indices is not yet understood. We aimed to investigate the association between ankle power and radiographic indices during gait in patients with CP concomitant with PV deformity. METHODS: Patients older than 14 years with ambulatory CP and PV deformity were included. All the patients underwent 3-dimensional gait analysis and weight-bearing foot radiography. Gait data were collected, including foot progression angle, tibial rotation, hip rotation, and ankle power generation. Radiographic measurements included anteroposterior (AP) talo-first metatarsal angle, lateral talo-first metatarsal angle, and hindfoot angle. A linear mixed-effects model was performed to identify significant radiographic indices associated with ankle power generation. RESULTS: Thirty-one limbs from 15 patients with spastic diplegia and 6 with spastic hemiplegia were included. Statistical analysis demonstrated that ankle power generation was significantly correlated with the CP type ( P =0.0068) and AP talo-1 st metatarsal angle ( P =0.0230). CONCLUSION: Ankle power generation was significantly associated with the AP talo-first metatarsal angle. Surgeons might need to pay attention to correcting forefoot abduction to restore ankle power when planning surgeries for pes PV deformities in patients with CP. LEVEL OF EVIDENCE: Prognostic Level III.

Intravitreal Administration of Retinal Organoids-Derived Exosomes Alleviates Photoreceptor Degeneration in Royal College of Surgeons Rats by Targeting the Mitogen-Activated Protein Kinase Pathway.

Increasing evidence suggests that exosomes are involved in retinal cell degeneration, including their insufficient release; hence, they have become important indicators of retinopathies. The exosomal microRNA (miRNA), in particular, play important roles in regulating ocular and retinal cell functions, including photoreceptor maturation, maintenance, and visual function. Here, we generated retinal organoids (ROs) from human induced pluripotent stem cells that differentiated in a conditioned medium for 60 days, after which exosomes were extracted from ROs (Exo-ROs). Subsequently, we intravitreally injected the Exo-RO solution into the eyes of the Royal College of Surgeons (RCS) rats. Intravitreal Exo-RO administration reduced photoreceptor apoptosis, prevented outer nuclear layer thinning, and preserved visual function in RCS rats. RNA sequencing and miRNA profiling showed that exosomal miRNAs are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway. In addition, the expression of MAPK-related genes and proteins was significantly decreased in the Exo-RO-treated group. These results suggest that Exo-ROs may be a potentially novel strategy for delaying retinal degeneration by targeting the MAPK signaling pathway.

Antioxidation and anti-inflammatory effects of gamma-irradiated silk sericin and fibroin in H2O2-induced HaCaT Cell.

Oxidative stress in skin cells can induce the formation of reactive oxygen species (ROS), which are critical for pathogenic processes such as immunosuppression, inflammation, and skin aging. In this study, we confirmed improvements from gamma-irradiated silk sericin (I-sericin) and gamma-irradiated silk fibroin (I-fibroin) to skin cells damaged by oxidative stress. We found that I-sericin and I-fibroin effectively attenuated oxidative stress-induced ROS generation and decreased oxidative stress-induced inflammatory factors COX-2, iNOS, tumor necrosis factor-α, and interleukin-1ß compared to the use of non-irradiated sericin or fibroin. I-sericin and I-fibroin effects were balanced by competition with skin regenerative protein factors reacting to oxidative stress. Taken together, our results indicated that, compared to non-irradiated sericin or fibroin, I-sericin, and I-fibroin had anti-oxidation and anti-inflammation activity and protective effects against skin cell damage from oxidative stress. Therefore, gamma-irradiation may be useful in the development of cosmetics to maintain skin health.

Intrasubject Radiographic Progression of Hallux Valgus Deformity in Patients With and Without Metatarsus Adductus: Bilateral Asymmetric Hallux Valgus Deformity.

This study was to analyze intrasubject radiographic progression of the hallux valgus deformity by comparing the mildly and severely affected sides in patients with bilateral asymmetric hallux valgus in the whole group as well as the metatarsus adductus and the nonmetatarsus adductus subgroups. A total of 186 patients with bilateral asymmetrical hallux valgus deformity with a difference of 5° or greater in the hallux valgus angle were included, and 11 radiographic measurements were analyzed. The radiographic differences between the mildly and severely affected sides were compared. Correlation between the changes in the hallux valgus angle and those in other measurements was analyzed, and multiple regression analyses were performed. The anteroposterior talo-second metatarsal angle showed no significant difference between the mildly and severely affected sides. Changes in the intermetatarsal angle and sesamoid rotation angle were significantly associated with the progression of hallux valgus angle in the whole group as well as the nonmetatarsus adductus subgroup. Change in the intermetatarsal angle (p = .006) was the significant factor associated with the progression of hallux valgus angle in the metatarsus adductus subgroup. The anteroposterior talo-second metatarsal angle might be useful in evaluating the overall foot shape in the hallux valgus deformity. Progression of the hallux valgus deformity might be pathophysiologically different between those with and without metatarsus adductus.

USO1 isoforms differentially promote liver cancer progression by dysregulating the ER-Golgi network.

Alternative splicing of RNA transcripts plays an important role in cancer development and progression. Recent advances in RNA-seq technology have made it possible to identify alternately spliced events in various types of cancer; however, research on hepatocellular carcinoma (HCC) is still limited. Here, by performing RNA-seq profiling of HCC transcripts at isoform level, we identified tumor-specific and molecular subtype-dependent expression of the USO1 isoforms, which we designated as a normal form USO1-N (XM_001290049) and a tumor form USO1-T (NM_003715). The expression of USO1-T, but not USO1-N, was associated with worse prognostic outcomes of HCC patients. We confirmed that the expression of USO1-T promoted an aggressive phenotype of HCC, both in vitro and in vivo. In addition, structural modeling analyses revealed that USO1-T lacks an ARM10 loop encoded by exon 15, which may weaken the dimerization of USO1 and its tethering to GM130. We demonstrated that USO1-T ensured unstacking of the Golgi and accelerated the vesicles trafficking from endoplasmic reticulum (ER) to Golgi and plasma membrane in multiple liver cancer cells. ERK and GRASP65 were found to be involved in the USO1-T-mediated Golgi dysfunction. Conclusively, we provide new mechanophysical insights into the USO1 isoforms that differentially regulate the ER-Golgi network, promoting the heterogeneous HCC progression.

TPRG1-AS1 induces RBM24 expression and inhibits liver cancer progression by sponging miR-4691-5p and miR-3659.

BACKGROUND & AIMS: Noncoding RNAs (ncRNAs) play critical roles in hepatocellular carcinoma (HCC) progression. Here, by performing RNA-sequencing (RNA-Seq) profiling, we sought to identify novel ncRNAs that potentially drive the heterogeneous progression of liver cancers. METHODS: RNA-Seq profiles were obtained from 68 HCC specimens and 10 samples of adjacent non-tumour liver tissues. The functional significance of the potential driver ncRNAs was evaluated by cell experiments. RESULTS: TPRG1-AS1 was identified as a potential driver noncoding RNA that promotes heterogeneous liver cancer progression. TPRG1-AS1 induced tumour suppressor RNA-binding motif protein 24 (RBM24), suppressing tumour growth by activating apoptotic tumour cell death. In addition, we report that TPRG1-AS1 acts as a competing endogenous RNA (ceRNA) for RBM24, sponging miR-4691-5p and miR-3659 to interfere with their binding to RBM24. CONCLUSIONS: We suggest that TPRG1-AS1 is a novel ceRNA sponging miR-4691-5p and miR-3659, resulting in RBM24 expression and suppression of liver cancer growth. Our results provide new insights into the functions of ncRNAs in heterogeneous HCC progression.

scTyper: a comprehensive pipeline for the cell typing analysis of single-cell RNA-seq data.

BACKGROUND: Recent advances in single-cell RNA sequencing (scRNA-seq) technology have enabled the identification of individual cell types, such as epithelial cells, immune cells, and fibroblasts, in tissue samples containing complex cell populations. Cell typing is one of the key challenges in scRNA-seq data analysis that is usually achieved by estimating the expression of cell marker genes. However, there is no standard practice for cell typing, often resulting in variable and inaccurate outcomes. RESULTS: We have developed a comprehensive and user-friendly R-based scRNA-seq analysis and cell typing package, scTyper. scTyper also provides a database of cell type markers, scTyper.db, which contains 213 cell marker sets collected from literature. These marker sets include but are not limited to markers for malignant cells, cancer-associated fibroblasts, and tumor-infiltrating T cells. Additionally, scTyper provides three customized methods for estimating cell-type marker expression, including nearest template prediction (NTP), gene set enrichment analysis (GSEA), and average expression values. DNA copy number inference method (inferCNV) has been implemented with an improved modification that can be used for malignant cell typing. The package also supports the data preprocessing pipelines by Cell Ranger from 10X Genomics and the Seurat package. A summary reporting system is also implemented, which may facilitate users to perform reproducible analyses. CONCLUSIONS: scTyper provides a comprehensive and user-friendly analysis pipeline for cell typing of scRNA-seq data with a curated cell marker database, scTyper.db.

Aggravation of Ankle Varus Incongruency Following Total Knee Replacement Correcting ≥10° of Genu Varum Deformity: A Radiographic Assessment.

BACKGROUND: This study aimed to investigate the change in ankle varus incongruencies following total knee replacement (TKR) in patients with preoperative genu varum deformity of ≥10°. METHODS: The study cohort was composed of patients who underwent TKR in a single institution for knee osteoarthritis with preoperative genu varum deformity of ≥10° and concomitant varus ankle incongruencies. Eight radiographic measurements were evaluated preoperatively and postoperatively: mechanical tibiofemoral angle, mechanical lateral distal femoral angle, medial proximal tibial angle, lateral distal tibial angle, tibial plafond inclination, talar inclination, tibiotalar tilt angle (TTTA), and tibia-mechanical axis angle. Of these, TTTA represented the quantitative degree of ankle joint incongruency. RESULTS: A total of 110 patients (male = 2; female = 108) were included in the analysis. The mean patient age was 68.9 (standard deviation [SD] 7.2) years at the time of TKR. All radiographic measurements showed significant changes postoperatively, representing the appropriate correction of genu varum deformity and restoration of the mechanical axis. Nineteen patients (17.3%) showed postoperative decrease in TTTA, 2 (1.8%) remained the same, and 89 (80.9%) showed increase. Overall, mean preoperative and postoperative TTTA were 3.3° (SD 2.2°) and 4.7° (SD 2.9°), respectively (P < .001), representing the aggravation of varus ankle incongruencies. CONCLUSION: Varus ankle incongruencies showed aggravation following TKR despite correction of genu varum deformity and restoration of the mechanical axis. This could be an important cause of postoperative increase or development of ankle pain following TKR. Therefore, patients with preoperative varus ankle incongruencies need to be warned of possible aggravation of ankle symptoms and be evaluated before TKR. LEVEL OF EVIDENCE: Prognostic level III.

SEQprocess: a modularized and customizable pipeline framework for NGS processing in R package.

BACKGROUNDS: Next-Generation Sequencing (NGS) is now widely used in biomedical research for various applications. Processing of NGS data requires multiple programs and customization of the processing pipelines according to the data platforms. However, rapid progress of the NGS applications and processing methods urgently require prompt update of the pipelines. Recent clinical applications of NGS technology such as cell-free DNA, cancer panel, or exosomal RNA sequencing data also require appropriate customization of the processing pipelines. Here, we developed SEQprocess, a highly extendable framework that can provide standard as well as customized pipelines for NGS data processing. RESULTS: SEQprocess was implemented in an R package with fully modularized steps for data processing that can be easily customized. Currently, six pre-customized pipelines are provided that can be easily executed by non-experts such as biomedical scientists, including the National Cancer Institute's (NCI) Genomic Data Commons (GDC) pipelines as well as the popularly used pipelines for variant calling (e.g., GATK) and estimation of allele frequency, RNA abundance (e.g., TopHat2/Cufflink), or DNA copy numbers (e.g., Sequenza). In addition, optimized pipelines for the clinical sequencing from cell-free DNA or miR-Seq are also provided. The processed data were transformed into R package-compatible data type 'ExpressionSet' or 'SummarizedExperiment', which could facilitate subsequent data analysis within R environment. Finally, an automated report summarizing the processing steps are also provided to ensure reproducibility of the NGS data analysis. CONCLUSION: SEQprocess provides a highly extendable and R compatible framework that can manage customized and reproducible pipelines for handling multiple legacy NGS processing tools.

Buforin-1 blocks neuronal SNARE-mediated membrane fusion by inhibiting SNARE complex assembly.

Assembly of neuronal SNARE protein complexes is essential for fusion of synaptic vesicles with the presynaptic plasma membrane, which releases neurotransmitters into the synaptic cleft and mediates neurotransmission. However, despite the potential of pharmacological regulation of this process for the treatment of various neurological disorders, only a few reagents, including botulinum neurotoxins, are currently available. Here, we report that buforin-1, an antimicrobial peptide from the Asian toad Bufo gargarizans, inhibits neuronal SNARE complex assembly, resulting in neuronal SNARE-mediated membrane fusion in vitro via its direct association with neuronal t-SNAREs syntaxin-1 and SNAP-25. Consistently, buforin-1 significantly inhibited neuronal-SNARE-mediated exocytosis in PC-12 cells. Thus, buforin-1 has potential for the treatment of neurological disorders caused by dysregulated neurotransmission.

Stool-Based miR-92a and miR-144* as Noninvasive Biomarkers for Colorectal Cancer Screening.

OBJECTIVES: Current noninvasive screening tests for colorectal cancer (CRC) have insufficient sensitivity. MicroRNA (miRNA) levels in stool have potential as markers for noninvasive screening of CRC. We evaluated the diagnostic value of stool miRNA levels and determined the optimal miRNA subtypes for detecting CRC. METHODS: Stool samples were collected from 29 patients with CRC and 29 healthy controls. The stool levels of miR-21, miR-92a, miR-200c, miR-144*, miR-135a, miR-135b, miR-106a, and miR-17-3p were determined by real-time quantitative reverse transcription polymerase chain reaction. The sensitivity and specificity of the miRNAs for CRC were determined by receiver operating characteristics analysis. RESULTS: Among the eight tested miRNAs, the mean stool levels of miR-21, miR-92a, miR-144*, and miR-17-3p differed significantly between the CRC group and the control group (p =0.014, 0.001, <0.001, and 0.008, respectively). The sensitivities and specificities of miR-21, miR-92, miR-144*, and miR-17-3p were 79.3 and 48.3%, 89.7 and 51.7%, 78.6 and 66.7%, and 67.9 and 70.8%, respectively. In a multivariate analysis, miR-92a and miR-144* were significantly associated with the presence of CRC (p = 0.03 and 0.011, respectively). CONCLUSIONS: The stool levels of miR-92a and miR-144* showed good sensitivity and fair specificity for detection of CRC, and thus may be useful as noninvasive biomarkers for this disease.

Does unicompartmental knee arthroplasty have worse outcomes in spontaneous osteonecrosis of the knee than in medial compartment osteoarthritis? A systematic review and meta-analysis.

INTRODUCTION: The role of unicompartmental knee arthroplasty (UKA) in spontaneous osteonecrosis of the knee (SONK) remains controversial, even though SONK involves only one compartment of the knee joint. We aimed to compare the survival rate and clinical outcomes of UKA in SONK and medial compartment osteoarthritis (MOA) via a meta-analysis of previous studies. MATERIALS AND METHODS: MEDLINE, Embase, and Cochrane Library were searched up to January 2018 with keywords related to SONK and knee arthroplasty. Studies were selected with predetermined inclusion criteria: (1) medial UKA as the primary procedure, (2) reporting implant survival or clinical outcomes of osteonecrosis and osteoarthritis, and (3) follow-up period > 1 year. Quality assessment was performed using the risk of bias assessment tool for non-randomized studies. A random-effects model was used to estimate the pooled relative risk (RR) and standardized mean difference. RESULTS: The incidence of UKA revision for any reason was significantly higher in SONK than in MOA group (pooled RR = 1.83, p = 0.009). However, the risk of revision due to aseptic loosening was not significantly different between the groups. Moreover, when stratified by the study quality, high-quality studies showed similar risk of overall revision in SONK and MOA (p = 0.71). Subgroup analysis revealed no significant difference in failure between SONK and MOA after cemented mobile and fixed bearing UKA. Results of uncemented UKA were reported only in one study, which showed higher failure of SONK compared to MOA. Clinical outcomes after UKA were similar between SONK and MOA (p = 0.66). CONCLUSIONS: Cemented UKA has similar survival and clinical outcomes in SONK and MOA. Prospective studies designed specifically to compare the UKA outcomes in SONK and MOA are necessary.

Pan-cancer analysis of systematic batch effects on somatic sequence variations.

BACKGROUND: The Cancer Genome Atlas (TCGA) is a comprehensive database that includes multi-layered cancer genome profiles. Large-scale collection of data inevitably generates batch effects introduced by differences in processing at various stages from sample collection to data generation. However, batch effects on the sequence variation and its characteristics have not been studied extensively. RESULTS: We systematically evaluated batch effects on somatic sequence variations in pan-cancer TCGA data, revealing 999 somatic variants that were batch-biased with statistical significance (P < 0.00001, Fisher's exact test, false discovery rate ≤ 0.0027). Most of the batch-biased variants were associated with specific sample plates. The batch-biased variants, which had a unique mutational spectrum with frequent indel-type mutations, preferentially occurred at sites prone to sequencing errors, e.g., in long homopolymer runs. Non-indel type batch-biased variants were frequent at splicing sites with the unique consensus motif sequence 'TTDTTTAGTT'. Furthermore, some batch-biased variants occur in known cancer genes, potentially causing misinterpretation of mutation profiles. CONCLUSIONS: Our strategy for identifying batch-biased variants and characterising sequence patterns might be useful in eliminating false variants and facilitating correct interpretation of sequence profiles.

Antioxidant Enzyme Activity, Iron Content and Lipid Oxidation of Raw and Cooked Meat of Korean Native Chickens and Other Poultry.

This study was conducted to observe antioxidant enzyme activity, iron content and lipid oxidation of Korean native chickens and other poultry. The breast and thigh meat of three Korean native chicken breeds including Woorimatdak, Hyunin black and Yeonsan ogye, and three commercial poultry breeds including the broiler, White Leghorn and Pekin duck (Anasplatyrhyncos domesticus) were studied. The analyses of the antioxidant enzymes activity, iron content and lipid oxidation were performed in raw and cooked samples. The activity of catalase (CAT) in the thigh meat was higher than that of the breast meat of three Korean native chickens and the broiler, respectively. The activity of glutathione peroxidase (GPx) in the uncooked thigh meat of three Korean native chickens was higher than that of the breasts. The breast meat of Woorimatdak and Pekin duck had higher superoxide dismutase (SOD) activity than the others, while only the thigh meat of Pekin duck had the highest activity. Cooking inactivated CAT and decreased the activity of GPx and SOD. The thigh meat of Woorimatdak, White Leghorn, Yeonsan ogye and Hyunin black contained more total iron than the breast meat of those breeds. The heme-iron lost during cooking ranged from 3.2% to 14.8%. It is noted that the thigh meat had higher thiobarbituric acid reactive substances values than the breast in all chicken breeds. Though Woorimatdak showed higher antioxidant enzyme activity and lower released-iron percentage among Korean native chickens, no differences were found on lipid oxidation. We confirm that the dark meat of poultry exhibited higher antioxidant enzyme activity and contained more iron than the white meat.

Mild one-pot Horner-Wadsworth-Emmons olefination and intramolecular N-arylation for the syntheses of indoles, all regio-isomeric azaindoles, and thienopyrroles.

The syntheses of various N-protected aromatic-ring fused pyrrole-2-carboxylate derivatives have been accomplished using mild one-pot Horner-Wadsworth-Emmons olefination and Cu-catalyzed intramolecular N-arylation reactions. The optimized mild one-pot reaction conditions of various 2-bromo arylcarboxaldehydes with commercially available N-protected phosphonoglycine trimethylesters gave the desired aromatic-ring fused pyrrole-2-carboxylates, such as substituted indole-, all regio-isomeric azaindole-, and thienopyrrole-2-carboxylates, in good to excellent yields. These conditions showed broad substrate compatibility, without the loss of the protecting group.